Estrogen receptor alpha targeting in liver cancer and breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA890176 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study is to identify estrogen receptor alpha targeting in liver cancer and breast cancer using RNA-Seq and ChIP-Seq and reveal the mechanisms underlying estrogen receptor alpha in the regulation of liver cancer and breast cancer.
2023-04-06 | GSE215384 | GEO
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells. RAR alpha silenced breast cancer MCF-7 cell lines or control siRNA in the presence of estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen for 12 h. There were three biological replicates for each of the four different groups.
2010-06-16 | E-GEOD-22213 | biostudies-arrayexpress
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.
2010-06-09 | GSE22213 | GEO
Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.
2020-09-02 | PXD018709 | Pride
Project description:Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer
| PRJNA548072 | ENA
Project description:Estrogen receptor α promotes breast cancer by reprogramming cell metabolism
| PRJNA298774 | ENA
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132428 | GEO
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132426 | GEO
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132424 | GEO
Project description:Cancer Associated Fibroblasts (CAFs) are crucial in the genesis and progression of tumors. Cervical CAFs (C-CAFs) are less well characterized. Estrogen (E2) is considered a cofactor in cervical carcinogenesis. We studied the molecular signature of exvivo cultured C-CAFs from 4 early International Federation of Gynaecology and Obstetrics (FIGO, IB2) and 2 late (IIIA) stage disease using gene expression microarray. We found C-CAFs to be both pro-tumorigenic and moderately inflammatory; late stage C-CAFs were more actively metabolizing, and cycling, but expressed fewer genes related to immune function. We investigated the expression of ERα in exvivo cultured C-CAFs and studied the role of E2 in their biology by gene expression microarray in the presence of two ERα antagonists: ICI 182,780 and Methyl Piperidino Pyrazole (MPP). Both modulated C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression, though their transcriptomes differed. MPP also down regulated genes involved in Epithelial to Mesenchymal Transition. Thus, canonical ERα signaling is vital for C-CAF functioning. Interfering with paracrine signaling through fibroblast ERα may be worth exploiting as a targeted therapy in cervical cancer. Gene expression microarray profiling of 4 early-stage E2 (estrogen) treated, 2 late-stage E2 treated, 2 early-stage ICI (ER-alpha antagonist) treated, 2 late-stage ICI treated and 2 early-stage MPP (ER-alpha antagonist) treated cervical cancer CAFs. E2 treated C-CAFs served as control.
2015-04-03 | E-GEOD-65227 | biostudies-arrayexpress